Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Depletion of tumor-associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin.

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.

Prognostic impact of soluble PD-L1 derived from tumor-associated macrophages in non-small-cell lung cancer.

Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.

Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer.

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non-small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I-IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors.

BACKGROUND: Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence. METHODS: The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for "mucus extension." RESULTS: The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019). CONCLUSIONS: During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.

Usability of the lateral decubitus position on four-dimensional ultra-low-dose computed tomography for the detection of localized pleural adhesion in the pulmonary apical region.

BACKGROUND: Localized pleural adhesion (LPA) evaluation in the apical region is difficult even with four-dimensional ultra-low-dose computed tomography (4D-ULDCT) in the supine position due to smaller pleural movements. PURPOSE: To assess usability of 4D-ULDCT in the lateral decubitus (LD) position for LPA detection in the apical region. MATERIAL AND METHODS: Forty-seven patients underwent 4D-ULDCT of a single respiration cycle with 16-cm coverage of body axis in supine and LD positions with the affected lung uppermost. Intraoperative thoracoscopic findings confirmed LPA presence. A pleural point and a corresponding point on costal outer edge were placed in identical axial planes at end-inspiration. Pleuro-chest wall distance between two points (PCD) was calculated at each respiratory phase. In the affected lung, average change in amount of PCD (PCDACA) was compared between patients with and without LPA in total and two sub-groups (non-COPD and COPD, non-emphysematous and emphysematous patients) in supine and non-dependent (ND) LD positions. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds in PCDACA for differentiating patients with LPA from those without. RESULTS: In COPD/emphysematous patients and total population, PCDACA with LPA was smaller than in those without in the supine and NDLD positions for overall, lateral, and dorsal regions. For the lateral region in COPD patients, area under ROC curve (AUC) increased from supine (0.64) to NDLD position (0.81). For the dorsal region in emphysematous patients, AUC increased from supine (0.76) to NDLD position (0.96). CONCLUSION: 4D-ULDCT in LD position may be useful for LPA detection in apical regions for COPD and/or emphysematous patients.

Dynamic perfusion digital radiography for predicting pulmonary function after lung cancer resection.

BACKGROUND: Accurate prediction of postoperative pulmonary function is important for ensuring the safety of patients undergoing radical resection for lung cancer. Dynamic perfusion digital radiography is an excellent and easy imaging method for detecting blood flow in the lung compared with the less-convenient conventional lung perfusion scintigraphy. As such, the present study aimed to confirm whether dynamic perfusion digital radiography can be evaluated in comparison with pulmonary perfusion scintigraphy in predicting early postoperative pulmonary function and complications. METHODS: Dynamic perfusion digital radiography and spirometry were performed before and 1 and 3 months after radical resection for lung cancer. Correlation coefficients between blood flow ratios calculated using dynamic perfusion digital radiography and pulmonary perfusion scintigraphy were then confirmed in the same cases. In all patients who underwent dynamic perfusion digital radiography, the correlation predicted values calculated from the blood flow ratio, and measured values were examined. Furthermore, ppo%FEV1 or ppo%DLco values, which indicated the risk for perioperative complications, were examined. RESULTS: A total of 52 participants who satisfied the inclusion criteria were analyzed. Blood flow ratios measured using pulmonary perfusion scintigraphy and dynamic perfusion digital radiography showed excellent correlation and acceptable predictive accuracy. Correlation coefficients between predicted FEV1 values obtained from dynamic perfusion digital radiography or pulmonary perfusion scintigraphy and actual measured values were similar. All patients who underwent dynamic perfusion digital radiography showed excellent correlation between predicted values and those measured using spirometry. A significant difference in ppo%DLco was observed for respiratory complications but not cardiovascular complications. CONCLUSIONS: Our study demonstrated that dynamic perfusion digital radiography can be a suitable alternative to pulmonary perfusion scintigraphy given its ability for predicting postoperative values and the risk for postoperative respiratory complications. Furthermore, it seemed to be an excellent modality because of its advantages, such as simplicity, low cost, and ease in obtaining in-depth respiratory functional information. TRIAL REGISTRATION: Registered at UMIN on October 25, 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000033957 Registration number: UMIN000029716.

Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients.

BACKGROUND: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). METHODS: Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system. RESULTS: CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratiohigh and VEGF-Chigh (M2 ratiohighVEGF-Chigh) was correlated with worse overall survival (p = 0.033). Multivariate analysis revealed that M2 ratiohigh [HR (95% CI) = 1.53 (1.01-2.33), p = 0.046] and combined M2 ratiohighVEGF-Chigh expression [HR (95% CI) = 2.01 (1.28-3.16), p = 0.003] were independent predictors of poor overall survival. Notably, we confirmed that M2 macrophages significantly enhanced the protein and mRNA expression of both VEGF-A and VEGF-C, while M1 macrophages induced only mRNA expression of VEGF-A in A549 cells. CONCLUSIONS: This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.

[Costochondritis and Osteomyelitis of the Ribs after Intercostal Thoracotomy].

A 53-year-old man underwent surgical repair and drainage of a spontaneous esophageal rupture through a left anterolateral intercostal thoracotomy. Thereafter, wound infection persisted for 3 years with formation of cutaneous fistulae and granulation tissue. Chest computed tomography revealed osteolysis, swollen ribs and costal cartilage, and cutaneous fistulous tracts. Bone scintigraphy with 99mTechnetium revealed abnormal accumulation in the ribs and costal cartilage, indicating costochondritis and osteomyelitis of ribs with cutaneous fistulae. Surgical resection of the skin including the cutaneous fistulae, infected ribs and costal cartilage were performed successfully.

[The Early Removal of the Implant after Nuss Procedure Due to the Infection in Case of Pectus Excavatum with Atopic Dermatitis].

Nuss procedure for pediatric patients with pectus excavatum has been practiced worldwide, including in Japan, due to the simple procedure and has a high therapeutic effect. Because it is usually performed under thoracoscopy to secure the safety, it is performed not only by pediatric or plastic surgeons but also by general thoracic surgeons. On the other hand, a risk of infection must always be considered in this method in which a foreign metal bar is used. In particular, when the skin barrier mechanism is declining due to skin diseases such as atopic dermatitis, the risk of infection of the implant may increase. The present case was an 8-year-old male with a history of atopic dermatitis. He underwent thoracoscopic Nuss procedure. Although there was no problem during his hospitalization, the bar was exposed from the skin on the 58th postoperative day with the infection triggered, and the unexpected early bar removal was performed on the 66th postoperative day. We report this case with some literature review.

Patient Survival after Surgical Management in Intrathoracic Pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, characterized by mucinous ascites and deposits diffusely present on the peritoneal surfaces. However, extension of PMP to the thoracic cavity is extremely rare. Although there are a few case reports on the long-term postoperative prognosis of intrathoracic lesions, whether surgical resection of these lesions can improve patient prognosis remains unclear. METHODS: We reviewed 17 patients with PMP who underwent resection of intrathoracic lesions after abdominal cytoreductive surgery and examined their clinical outcome after surgery. RESULTS: Direct extension into the pleural cavity was identified in 11 patients. Extrapleural pneumonectomy of the lesions followed by hyperthermic intrathoracic chemotherapy (HITOC) was performed in four patients, parietal pleurectomy and visceral tumor resection followed by HITOC in four patients, resection of all disseminated pleural and visceral lesions followed by HITOC in one patient, resection of a single disseminated lesion in one patient, and composite resection of basal segment with the diaphragm in one patient. Pulmonary metastases were found in six patients. Partial resection was performed in four patients, segmentectomy in one patient, and lobectomy in one patient. We could perform macroscopic resection of the tumor in all the cases. The 5-year overall survival rate after thoracic surgery for the 17 patients was 46.1% and relapse-free survival was 34.9%. CONCLUSIONS: Resection of intrathoracic lesions of PMP after abdominal cytoreductive surgery achieved 5 years survival in at least 46.1% of the patients. Aggressive tumor resection should be considered for patients with PMP extending to thoracic cavity.

[The Outcome and Surgical Strategy of Segmentectomy for c-T1 Lung Cancer].

OBJECTIVES: Segmentectomy has been performed as an alternative surgical procedure for small-size lung cancer, while its benefits and risks are still unclear. This retrospective study aimed to examine the outcomes of patients undergoing segmentectomy for early stage lung cancer. PATIENTS AND METHODS: From 2010 to 2018, 90 patients with clinical-T0/1N0M0 lung cancer who underwent segmentectomy were enrolled. We analyzed the postoperative morbidity, tumor recurrence and survival rate after surgery. RESULTS: Postoperative complications were observed in 9 patients, and significant difference was found in passive limited surgery (p=0.003). Recurrence was observed in 4 patients, and pathological vessel invasion was a significant risk factor( p=0.035), but there was no local recurrence. The 5-year overall survival rate for all patients, active and passive limited surgery group were 90.7%, 91.5% and 58.0%, respectively. There was significant difference in surgical indication( p<0.001). CONCLUSIONS: Active segmentectomy which had considered the tumor characteristics was able to obtain a good tumor control effect by combining adjacent lung resection. Passive segmentectomy should be determined after careful consideration of the effects on comorbidities.

[The Outcome of Video Assisted Thoracoscopic Combined Subsegmentectomy].

PURPOSE: This study aimed to examine retrospectively the outcome of patients undergoing subsegmentectomy for malignant lung tumor. PATIENTS AND METHOD: From 2011 to 2017, 11 patients were enrolled. We analyzed the clinicopathologic data, radiological tumor findings, and postoperative morbidity. Overall survival of primary lung cancer was also assessed. RESULTS: Nine patients with primary lung cancer and 2 patients with metastatic lung cancer were diagnosed. There were no serious postoperative complications. All patients had negative surgical margins and were free from local recurrence. Lung adenocarcinoma was confirmed in 9 patients, who all had early stage and 5-year overall survival rate was 89%. CONCLUSIONS: Combined subsegmentectomy leads good results for small malignant lung tumor with tolerable complications.

Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer patients with lymph node metastasis.

BACKGROUND: The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is considered to be a major driver of lymphangiogenesis, however the mechanism of this process remains unclear. We aimed to investigate the possible lymphangiogenic significance of synaptonemal complex protein 3 (SCP3) in non-small cell lung cancer (NSCLC). METHODS: The expression of SCP3, VEGF-C, and VEGF-D were measured and examined a correlation between SCP3 and VEGF-C or VEGF-D in various human lung cancer cell lines. Subsequently, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expression in archival tumor tissues from 89 NSCLC patients with lymph node (LN) metastasis by combined immunohistochemistry with quantitative digital image analysis. RESULTS: Positive correlations between SCP3 and VEGF-C expression (R 2  = 0.743) and VEGF-D expression (R 2  = 0.932) were detected in various human lung cancer cell lines. The high expression of SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, SCP3 positively correlated with VEGF-C and VEGF-D expression (for both, P < 0.001) and negatively correlated with VEGF-A and VEGF-B expression (P = 0.029 and P = 0.026, respectively). In multivariate analysis of patients with LN metastasis, SCP3 expression predicted worse overall survival (hazard ratio = 1.86, P = 0.008). CONCLUSIONS: SCP3 is associated with lymphangiogenesis and provides insight into the SCP3-VEGF-C/VEGF-D axis based cancer therapy strategy.

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis.

Leptomeningeal metastases occur in 1% of patients with non-small-cell lung cancer. There have been several reports on the treatment of leptomeningeal metastases with afatinib. Our patient was a 41-year-old woman who had never smoked and was diagnosed with stage IV adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation. She was treated with afatinib for the recurrence of leptomeningeal metastases. After the treatment with afatinib was initiated, the neurological symptoms dramatically regressed, and she achieved progression-free survival for 7 months. The concentration of afatinib in the cerebrospinal fluid (CSF) ranged from 0.05 to 0.14 ng/mL, and the penetration rate of afatinib from the plasma to the CSF ranged from 0.28 to 0.40%. This concentration might be sufficient to achieve a clinical effect for leptomeningeal carcinomatosis. Therefore, afatinib administered at the usual doses may be an effective treatment for leptomeningeal carcinomatosis of EGFR-mutated or EGFR-tyrosine kinase inhibitor-sensitive lung adenocarcinoma.

Energy metabolism and nutritional status in hospitalized patients with lung cancer.

This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris-Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in dendritic cell-based vaccine.

Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME-targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer-associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro-tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor-associated immune responses by CAF-targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti-fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid-derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell-derived factor-1, prostaglandin E2 , and transforming growth factor-ß. In tumor-draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor-associated antigen-specific CD8(+) T cells. In addition, CAF-targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8(+) T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell-based vaccines; however, the suppressive effect on tumor growth was not observed in tumor-bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF-targeted therapy, and these effects are enhanced when combined with effector-stimulatory immunotherapy such as dendritic cell-based vaccines. Our mouse model provides a novel rationale with TME-targeted strategy for the development of cell-based cancer immunotherapy.

Detection of Lymph Nodes Metastasis in Biliary Carcinomas: Morphological Criteria by MDCT and the Clinical Impact of DWI-MRI.

BACKGROUND/AIMS: This study was conducted to assess the usefulness of multi-slice CT (MDCT) and diffusion weighted MR images (DWI-MRI) for diagnosis of metastatic lymph nodes (LNs) in biliary carcinomas. METHODOLOGY: Eighteen patients with biliary carcinomas (total 121 LNs) underwent surgical resection were included. In MDCT, the following criteria were measured: the maximum diameter, the enhanced value and the long and short axis (L/S) ratio. In DWI-MRI, the apparent diffusion coefficients (ADCs) were measured from ADC maps. RESULTS: In ROC analysis, the maximum diameter has the highest diagnostic power with area under curves of 0.903. And when the maximum diameter 8 mm and L/S ratio is less than 2, the accuracy was improved with a sensitivity of 81%, positive predictive value (PPV) of 45%. In DWI-MRI, ADCs values of metastatic LNs significantly lower than that of non-metastatic LNs (mean: 1.65 vs. 2.11 x10 3mm2/s). When the ADC value of 1.8 x10(-3) was used as a cut-off value, the best results were obtained with sensitivity of 75%, PPV of 82%. CONCLUSIONS: Using MDCT, diagnosis of LNs metastasis should be more than 8mm diameter and less than 2 of L/S ratio. In addition, DWI-MRI is more useful modality for diagnosis of LNs metastasis.

Minimally invasive surgery using the open magnetic resonance imaging system combined with video-assisted thoracoscopic surgery for synchronous hepatic and pulmonary metastases from colorectal cancer: report of four cases.

Simultaneous resection of hepatic and pulmonary metastases (HPM) from colorectal cancer (CRC) has been reported to be effective, but it is also considered invasive. We report the preliminary results of performing minimally invasive surgery using the open magnetic resonance (MR) imaging system to resect synchronous HPM from CRC in four patients. All four patients were referred for thoracoscopy-assisted interventional MR-guided microwave coagulation therapy (T-IVMR-MCT) combined with video-assisted thoracoscopic surgery (VATS). The median diameters of the HPM were 18.2 and 23.2 mm, respectively. The median duration of VATS and T-IVMR-MCT was 82.5 and 139 min, respectively. All patients were discharged without any major postoperative complications. One patient was still free of disease at 24 months and the others died of disease progression 13, 36, and 47 months without evidence of recurrence in the treated area. Thus, simultaneous VATS + T-IVMR-MCT appears to be an effective option as a minimally invasive treatment for synchronous HPM from CRC.

Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver.

AIM: This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver. METHODS: Male Wistar rats were subjected to 30 min of warm hepatic ischemia followed by immediate p.o. intake of enteral nutrition with WHP (HWP group) or 20% glucose solution (control group) (0.025 mL/g). The animals were killed at 6 or 12 h after reperfusion. The serum aspartate aminotransferase (AST) and alanine aminotransferase alt (ALT) levels were measured. The necrotic areas were assessed histologically. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activation were assessed to evaluate apoptosis. The expressions of hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nuclear factor (NF)-κB in the liver tissue were assessed by real time reverse transcription polymerase chain reaction. RESULTS: Significant reductions in the serum AST and ALT levels were seen in the HWP group compared with the control group at both 6 and 12 h after reperfusion. The necrotic areas and numbers of TUNEL positive cells were significantly decreased in the HWP group at 6 and 12 h after reperfusion. The caspase-3/7 activities were significantly decreased in HWP group at 6 and 12 h after reperfusion. The mRNA expressions of TNF-α and IL-6 were significantly reduced in the HWP group at 12 h after reperfusion. NF-κB mRNA expression was significantly increased in the HWP group at 6 and 12 h after reperfusion. CONCLUSION: Enteral nutrition containing HWP ameliorated the hepatic warm I/R injury possibly through the suppression of pro-inflammatory cytokine expressions and the induction of NF-κB in the rat liver.